Abstract
Intestinal barrier dysfunction remains a critical problem in patients with intracerebral hemorrhage (ICH) and is associated with poor prognosis. Ghrelin, a brain-gut peptide, has been shown to exert protection in animal models of gastrointestinal injury. However, the effect of ghrelin on intestinal barrier dysfunction post-ICH and its possible underlying mechanisms are still unknown. This study was designed to investigate whether ghrelin administration attenuates intestinal barrier dysfunction in experimental ICH using an intrastriatal autologous blood infusion mouse model. Our data showed that treatment with ghrelin markedly attenuated intestinal mucosal injury at both histomorphometric and ultrastructural levels post-ICH. Ghrelin reduced ICH-induced intestinal permeability according to fluorescein isothiocyanate conjugated-dextran (FITC-D) and Evans blue extravasation assays. Concomitantly, the intestinal tight junction-related protein markers, Zonula occludens-1 (ZO-1) and claudin-5 were upregulated by ghrelin post-ICH. Additionally, ghrelin reduced intestinal intercellular adhesion molecule-1 (ICAM-1) expression at the mRNA and protein levels following ICH. Furthermore, ghrelin suppressed the translocation of intestinal endotoxin post-ICH. These changes were accompanied by improved survival rates and an attenuation of body weight loss post-ICH. In conclusion, our results suggest that ghrelin reduced intestinal barrier dysfunction, thereby reducing mortality and weight loss, indicating that ghrelin is a potential therapeutic agent in ICH-induced intestinal barrier dysfunction therapy.
Highlights
Intracerebral hemorrhage (ICH) is the most devastating subtype of stroke and is associated with high morbidity and mortality
The increased permeability of injured intestinal mucosa could result in the translocation of intestinal endotoxin, which, in turn, triggers both a systemic inflammatory response syndrome (SIRS) and a multiple organ dysfunction syndrome (MODS)
intercellular adhesion molecule-1 (ICAM-1) contributes to intestinal barrier dysfunction and cytokine release, which is positively correlated with injury severity [13]
Summary
Intracerebral hemorrhage (ICH) is the most devastating subtype of stroke and is associated with high morbidity and mortality. This hemorrhagic disorder accounts for 10%–15% of all strokes, with approximately 2 million cases per year worldwide [1]. Intestinal barrier dysfunction is a common complication after ICH that leads to malabsorption, malnutrition, hypoimmunity, and poor prognosis in patients [2,3]. Intestinal barrier dysfunction is mainly characterized by mucosal injury and increased intestinal permeability [4,5]. Effective strategies for preventing intestinal barrier dysfunction following ICH are still lacking [7]. Until now, no study has addressed the potential effect of ghrelin on ICH-induced intestinal barrier dysfunction. Our study was conducted to test the hypothesis that ghrelin administration attenuates intestinal barrier impairment following ICH in mice
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